DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant’s amendments to the claims of March 2, 2026, in response to the Office Action of November 3, 2025, are, acknowledged.
Response to Arguments
The § 112 Rejections are withdrawn in view of the amendments to the claims. The examiner also withdraws the § 102 rejection in view of the picking and choosing required to arrive at the combination claimed. In particular, the routes of administration described by the prior art include any route while the instant claims required SQ administration.
With respect to the rejection under § 103, Applicant argues that there are unexpectedly improved properties associated with the claimed method. In particular, Applicant argues that elobixibat results in a higher plasma concentration when administered subcutaneously as compared to orally. Applicant shows that “plasma exposed to elobixibat was considerably higher after s.c. administration compared to oral administration.” On this bases of overall better bioavailability shown through a couple different parameters, Applicant argues that unexpected results have been shown to obviate the rejection of record.
The examiner notes that a prima facie showing is established because the prior art teaches administering ASBT inhibitors including odevixibat and elobixibat to a subject with a variety of bile acid dependent diseases and wherein administration can be made subcutaneously. See par.’s 8, 9, 122, 558, 607, and others. While the examiner does believe that the prior art teaches each of the claimed limitations, he is not making an anticipatory rejection based on some level of picking and choosing required.
In this case, Applicant has claimed a variety of ASBT inhibitors. The allegations of unexpected results are directed to increased bioavailability of a single drug, elobixibat. Even if shown, the results would not be commensurate in scope with the claims because the claims are not limited to elobixibat.
More substantively, Applicant argues that SQ administration yields an unexpectedly higher bioavailability. The examiner cites the following: https://howmed.net/pharmacology/bioavailability-of-drugs/ “Bioavailability of Drugs,” September 4, 2011, which indicates the following with respect to generic bioavailability data in view of different routes of administration.
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In view of the above, which is explained more below, SQ administration is expected to provide substantially greater bioavailability than oral administration. As such, it is not clear how Applicant’s showing is unexpected.
The article further explains the known reasons for this include entering systemic circulation without intestinal and bacterial metabolism and first pass metabolism, which occurs in the liver after an oral drug enters the portal circulation. Subcutaneously administered drugs are known to by-pass first pass metabolism.
As such, the plasma concentration of a subcutaneously administered drug and the results occurring as a result of higher bioavailability do not appear unexpected. Further, if they were shown to be unexpected, those results nonetheless remain limited to a specific drug and the claims are not so limited. As such, the prima facie showing of obviousness is set forth below and consistent with this showing (as described below), many of the DP rejections are maintained.
With respect to the traversal of DP rejections, the examiner notes that the ‘226 patent is directed to administration of odevixibat formulations that formulated for use in treating bile-acid dependent liver diseases. In view of Jaecklin et al., (US20220160726), the instantly claimed method would be obvious.
Similarly, the ‘046 patent is directed to a product of odevixibat that is described to treat bile acid dependent diseases. In view of Jaecklin et al., (US20220160726), the instantly claimed method would be obvious.
The rejection under the ‘394 patent is withdrawn.
The ‘182 patent is directed to a different route of administering the same drug to the same subject population. See claims 1 and 8. In view of Jaecklin any route of administration would be contemplated.
The ‘539 patent is drawn to treating a bile acid dependent liver disorder by administering odevixibat. In view of Jaecklin a POSA would understand that other routes of administration can be used.
Similarly, the ‘156 patent is drawn to treating a bile acid dependent liver disorder by administering odevixibat. In view of Jaecklin a POSA would understand that other routes of administration can be used.
The provisional rejection over 18/535,313 is also maintained in view of Jaecklin as the claims are directed to treating any renal disease or bile acid dependent disorder with an ASBT inhibitor.
Status of the Claims
Claims 32-34, 36, and 38-64 are pending. Claims 36, 38 and 40-52 are withdrawn. Claims 32-34, 39, and 53-64 are examined.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 32-34, 39, and 53-64 are rejected under 35 U.S.C. 103 as being unpatentable over Jaecklin et al., (US20220160726)(filed February 12, 2020).
Jaecklin teaches treating cholestasis by administering an ASBT inhibitor at a dosage of at least 10 micrograms/kg/day. See Abstract. The ABSTI inhibitor can be odevixibat or a salt thereof, among a limited list of agents. See par. 7. The route of administration includes parenteral injection, including subcutaneous. See par.’s 122, 558, and 607. In some embodiments, a formulation can be for non-systemic delivery if administered orally. See par. 603. Such non-systemic means less than 5%, e.g., is administered systemically. See par. 132. Formulations are designed for less than 10% systemic delivery. See par. 133. A single dose can be delivered every 24 hours, e.g. This is interpreted as once daily. See par. 563. A reduction is symptoms includes a reduction in serum bile acid concentration. See par. 11. Liver enzyme ALT can be shown to decrease relative to baseline. See prior art claim 45, e.g. Bilirubin, ALT, and serum bile acid was shown in clinical study. See par. 744. Levels of ALT, AST, and bilirubin concentrations normalized over time. See par. 744. Administration can be for at least 4 weeks. See par. 579.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With regard to claims 54-64, the claims are directed to a result of the claimed agent being administered by the claimed route of administration to a claimed subject population. Absent evidence to the contrary and limitations in the claims that distinguish, these descriptions are considered results of a step of administration that has been positively recited and a product of an optimized administration of a claimed agent. According to M.P.E.P. § 2111.04, “a ‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
The examiner notes that there do not appear to be additional limitations other than those claimed in the claims from which claims 54-64 depend as the Specification provides examples in which elobixibat was administered to mice.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Jaecklin. One would be motivated to do so because Jaecklin teaches administering the claimed agent to the claimed subject through the claimed route of administration for the claimed time period. The API is a known result-effective variable that can be optimized through nothing more than routine experimentation. Even further, the same biomarkers were taught to be evaluated, which would further aid in optimization. As such, there is a reasonable and predictable expectation of success in arriving at the claimed methods in view of Jaecklin.
Claims 32-34, 39, and 53-64 are rejected under 35 U.S.C. 103 as being unpatentable over Jaecklin et al., (US20220160726)(filed February 12, 2020), in view of Lundqvist et al., (U.S. Pat. No. 10,975,046) (published April 13, 2021).
Jaecklin teaches treating cholestasis by administering an ASBT inhibitor at a dosage of at least 10 micrograms/kg/day. See Abstract. The ABSTI inhibitor can be odevixibat or a salt thereof, among a limited list of agents. See par. 7. The route of administration includes parenteral injection, including subcutaneous. See par.’s 122, 558, and 607. In some embodiments, a formulation can be for non-systemic delivery if administered orally. See par. 603. Such non-systemic means less than 5%, e.g., is administered systemically. See par. 132. Formulations are designed for less than 10% systemic delivery. See par. 133. A single dose can be delivered every 24 hours, e.g. This is interpreted as once daily. See par. 563. A reduction is symptoms includes a reduction in serum bile acid concentration. See par. 11. Liver enzyme ALT can be shown to decrease relative to baseline. See prior art claim 45, e.g. Bilirubin, ALT, and serum bile acid was shown in clinical study. See par. 744. Levels of ALT, AST, and bilirubin concentrations normalized over time. See par. 744. Administration can be for at least 4 weeks. See par. 579.
Further, Lundqvist teaches odevixibat for treating liver diseases associated with elevated bile acid levels. The crystalline hydrate form of odevixibat would be obvious to use in the methods described by Jaecklin. As such, PK parameters that flow directly from the use of crystalline forms of odevixibat, including those described by Lundqvist.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With regard to claims 54-64, the claims are directed to a result of the claimed agent being administered by the claimed route of administration to a claimed subject population. Absent evidence to the contrary and limitations in the claims that distinguish, these descriptions are considered results of a step of administration that has been positively recited and a product of an optimized administration of a claimed agent. According to M.P.E.P. § 2111.04, “a ‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
The examiner notes that there do not appear to be additional limitations other than those claimed in the claims from which claims 54-64 depend as the Specification provides examples in which elobixibat was administered to mice.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Jaecklin and Lundqvist. One would be motivated to do so because Jaecklin teaches administering the claimed agent to the claimed subject through the claimed route of administration for the claimed time period. It would be further obvious to use a crystalline form of the same API to the extent that claimed parameters derive from such crystalline form. The API is a known result-effective variable that can be optimized through nothing more than routine experimentation. Even further, the same biomarkers were taught to be evaluated, which would further aid in optimization. As such, there is a reasonable and predictable expectation of success in arriving at the claimed methods in view of Jaecklin and Lundqvist.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 32-34, 39, and 53-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,801,226, in view of Jaecklin et al., (US20220160726).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘226 patent are directed to a crystalline hydrate of odevixibat and Jaecklin teaches using odevixibat for treating the claimed subject population. In view of Jaecklin it would be obvious to administer the composition taught by the ‘226 patent to a subject described by Jaecklin. As such, there is a reasonable and predictable expectation of success in arriving at the instant claims in view of the ‘226 patent.
Claims 32-34, 39, and 53-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,975,046, in view of Jaecklin et al., (US20220160726).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘046 patent are directed to a crystalline hydrate of odevixibat and Jaecklin teaches using odevixibat for treating the claimed subject population. In view of Jaecklin it would be obvious to administer the composition taught by the ‘046 patent to a subject described by Jaecklin. As such, there is a reasonable and predictable expectation of success in arriving at the instant claims in view of the ‘046 patent.
Claims 32-34, 39, and 53-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,365,182, in view of Jaecklin et al., (US20220160726).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘182 patent are directed to a crystalline hydrate of odevixibat to treat liver diseases, including cholestasis. In view of Jaecklin it would be obvious to administer the same subcutaneously. The instant claims are broader than the crystalline form and would be expected to work as it is the same API taught for administration. As such, there is a reasonable and predictable expectation of success in arriving at the instant claims in view of the ‘182 patent.
Claims 32-34, 39, and 53-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,583,539, in view of Jaecklin et al., (US20220160726).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘539 patent are directed to a crystalline hydrate of odevixibat to treat liver diseases, including cholestasis. In view of Jaecklin it would be obvious to administer the same subcutaneously. The instant claims are broader than the type of cholestasis claimed in the ‘539 patent, but it would be expected to work as it is the same API taught for administration. As such, there is a reasonable and predictable expectation of success in arriving at the instant claims in view of the ‘539 patent.
Claims 32-34, 39, and 53-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 12,447,156, in view of Jaecklin et al., (US20220160726).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘156 patent are directed to a crystalline hydrate of odevixibat to treat liver diseases, including cholestasis. In view of Jaecklin it would be obvious to administer the same subcutaneously. The instant claims are broader than the type of cholestasis claimed in the ‘539 patent (which is associated with pruritus), but it would be expected to work as it is the same API taught for administration. Further, the subject has cholestasis and the claimed API is taught to treat cholestasis with or without pruritus. As such, there is a reasonable and predictable expectation of success in arriving at the instant claims in view of the ‘156 patent.
Claims 32-34, 39, and 53-64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-25 of copending Application No. 18/535,313. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘313 application are directed to treating a renal disorder by administering an ASBT inhibitor. The route of administration is broad and includes subcutaneous administration (see claim 9). The results of administration are claimed in both the instant application and the ‘313 application. As such, it would be obvious to arrive at the instant claims in view of the claims of the ‘313 application and vice versa.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
As such, no claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628